Contrast Media (hereinafter "CM") are routinely used in various imaging procedures. Such procedures include visualization of blood vessels in cardiac angiography, either by x-ray imaging or by Magnetic Resonance Imaging (MRI), intravenous urography (kidney imaging), computerized tomography and neurologic visualization of the spinal cord, the brain, etc. In the U.S.A. alone, there are more than 10 million x-ray radiologic examinations using CM, performed each year. 5 to 10% of these procedures are accompanied by clinical side effects; in 1 out of 1000-2000 of such procedures, there occurs a life threatening complication.
The currently used CM in the x-ray imaging procedure can be grouped, on the basis of their osmolarity, to such which have a low osmolarity (hereinafter "LOCN") and such having a high osmolarity (hereinafter "HOCM"). It should be noted that both LOCM and HOCM have an osmolarity which is above that of the blood. HOCM have a typical osmolarity of about 1500-2000 mOsm/kg and LOCM have an osmolarity within the range of 300-700 mOsm/kg. Adverse side effects associated with CMs include such which result from the high osmolarity. The introduction of LOCMs, which are the new generation of CMs, was meant to counter some of these side effects. It should be noted that one big disadvantage of LOCMs is their high price-tag (about 5-10 times that of HOCM). Therefore, there is a dispute of the kinds of x-ray CMs which should be used.sup.(1).
The visualization which is the outcome of CM injection into the blood, results from a local dispersion of the high iodine atom concentration contained in the CM, from the high osmolarity, as well as from an increased viscosity in the blood vessels of the visualized organ.sup.(2). In procedures wherein the CMs are introduced into the blood, this is achieved either by injection into the blood vessels or by catheterization.
The MRI method for visualization of blood vessels comprises the injection of a paramagnetic substance dissolved in a hyperosmotic CM to the region to be visualized.
Individuals subjected to procedures involving the use of CMs, are exposed to several hazards, depending on the CM used, including:
1. Hyperosmotic Damage:
Typically 100-200 ml of CM are injected into a total plasma volume of 5 liters within a period of several minutes. Cells such as endothelial cells, red and white blood cells, cells within the kidney, etc., are exposed to a hyperosmotic solution, reaching 200-2000 mOsm/kg at the site of injection, as compared to the osmolarity of the blood with its 300 mOsm/kg, giving rise to a hyperosmotic shock which may elicit related damages. In the following description the term "hyperosmotic CM" will refer to any CM having osmolarity higher than the blood osmolarity which is typically 300 mOsm/kg.
2. Iodine Specific Toxicity:
In an x-ray visualization procedure typically 30-40 grams of iodine (included within the contrast media) are injected into the blood within the period of 2-10 minutes. It should be noted that target visualization requires a minimum accumulation of 15-20 mg of iodine/ml in the target tissue.sup.(3) and this is the reason that the initial iodine concentration in the CM is relatively high in the range of 300-420 mg iodine/ml.
3. Kidney Damage:
The iodine load to which the kidney is exposed and which it has to secrete is a potential cause for renal damage.sup.(4). It is generally believed today that 12% of all patients which are injected with an x-ray CM, encounter renal complications.sup.(5). A recent study shows that during cardiac catheterization procedure, 9% of low risk and 16% of high risk patients develop renal failure.sup.(6). Various studies made with CMs have shown that exposure of cells to x-ray CM causes the cell damages.sup.(7,8,9.10).